Analysis of Mitochondrial haemoglobin in Parkinson's disease brain.
Mitochondrial dysfunction is an early feature of neurodegeneration. We
have shown there are mitochondrial haemoglobin changes with age and
neurodegeneration. We hypothesised that altered physiological processes
are associated with recruitment and localisation of haemoglobin to these
organelles. To confirm a dynamic localisation of haemoglobin we exposed
Drosophila melanogaster to cyclical hypoxia with recovery. With a
single cycle of hypoxia and recovery we found a relative accumulation of
haemoglobin in the mitochondria compared with the cytosol. An
additional cycle of hypoxia and recovery led to a significant increase
of mitochondrial haemoglobin (p$_amp_$lt;0.05). We quantified ratios of
human mitochondrial haemoglobin in 30 Parkinson's and matched control
human post-mortem brains. Relative mitochondrial/cytosolic quantities of
haemoglobin were obtained for the cortical region, substantia nigra and
cerebellum. In age matched post-mortem brain mitochondrial haemoglobin
ratios change, decreasing with disease duration in female cerebellum
samples (n=7). The change is less discernible in male cerebellum (n=18).
In cerebellar mitochondria, haemoglobin localisation in males with long
disease duration shifts from the intermembrane space to the outer
membrane of the organelle. These new data illustrate dynamic
localisation of mitochondrial haemoglobin within the cell. Mitochondrial
haemoglobin should be considered in the context of gender differences
characterised in Parkinson's disease. It has been postulated that
cerebellar circuitry may be activated to play a protective role in
individuals with Parkinson's. The changing localisation of intracellular
haemoglobin in response to hypoxia presents a novel pathway to
delineate the role of the cerebellum in Parkinson's disease.
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